Nerve guide conduits promote nerve regeneration under a combination of electrical stimulation and RSCs combined with stem cell differentiation

Abstract

Nerve guide conduits (NGCs) offer a promising alternative to traditional tools for regenerating peripheral nerves. The efficacy of nerve regeneration and functional recovery is heavily dependent on the electrical, chemical, and physical properties of NGCs. A bionic melt electrowriting (MEW) NGC loaded with placental derived mesenchymal stem cells (PDMSCs) has been developed. Our study introduces a novel approach by utilizing Schwann cells induced from placental mesenchymal stem cells (PDMSCs), showcasing their potential in enhancing nerve regeneration when integrated with conductive nerve guidance conduits. Schwann cells (SCs) are crucial for nerve regeneration, and while various stem cells, including bone marrow stromal cells (BMSCs), have been investigated as sources of SCs for NGC loading, they are often limited by ethical concerns and restricted availability. PDMSCs, however, offer the advantages of widespread sourcing and unique ability to differentiate into SCs, making them an attractive alternative for NGC applications. This NGC utilizes an electrostatic direct writing technique employing polycaprolactone (PCL) for the sheath and a crimped fiber scaffold made of polypyrrole (PPY) incorporated with PDMSCs for its internal structure. The bionic PC-NGC loaded with PDMSCs exhibits favorable characteristics including permeability, mechanical stability, and electrical conductivity. The PPY component effectively transmits physiological nerve signals, thereby promoting nerve regeneration, while the PDMSCs differentiate into Schwann cells, creating a conducive environment for nerve regeneration. This research innovatively combines PDMSCs, known for their wide availability and SC differentiation potential, with a bionic NGC to enhance the treatment of peripheral nerve injuries (PNIs). In vitro evaluations have confirmed the excellent biocompatibility of the materials used. Animal experiments using a rat model with sciatic nerve injury demonstrated that the PC-NGC significently facilitated peripheral nerve regeneration. This was evidenced by improvements in axonal myelination, increased muscle mass, enhanced sciatic nerve function index, and positive electrophysiological findings. These outcomes are comparable to those achieved through autologous transplantation. Characterized by its layered oriented fibers, the bionic PC-NGC integrates multi-scale and multifunctional biomaterials with PDMSCs to effectively address peripheral nerve injuries (PNIs). The use of this printed NGC stimulates neuronal cell growth, thereby accelerating nerve regeneration. This innovative approach in tissue engineering presents a promising clinical treatment strategy for PNIs.